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Identification of a human organic anion transporter (hORCTL3, SLC22A13) facilitating urate and high affinity nicotinate exchange in kidney and intestine
Author(s) -
Hagos Yohannes,
Burckhardt Gerhard,
Bahn Andrew
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a910
Subject(s) - chemistry , organic anion transporter 1 , kidney , xenopus , transporter , urine , large intestine , biochemistry , small intestine , biology , endocrinology , gene
Organic Anion Transporters (OATs) are important for the secretion of endogenous metabolites, xenobiotics and drugs into the urine. Recently, a cDNA coding for 551 amino acids was identified and called hORCTL3. Tissue distribution examined by RT‐PCR analysis revealed a strong expression of one splice variant of hORCTL3 in the kidneys, whereas another splice variant was ubiquitously expressed including intestine and colon. hORCTL3‐expressing Xenopus laevis oocytes showed a substantial uptake of [ 3 H] p ‐aminohippurate as well as [ 14 C]urate. A comparison of the driving forces of hORCTL3 with hURAT1 and hOAT4, the apical urate exchangers, exhibited a significant inhibition of hORCTL3‐mediated [ 14 C]urate uptake by L‐lactate, pyrazinoate and nicotinate similar to hURAT1. However, trans ‐stimulation studies revealed only pyrazinoate to enhance [ 14 C]urate uptake to a significant extent, indicating an exchange mode of action for hORCTL3. To further support this idea, we performed hORCTL3‐mediated [ 3 H]nicotinate uptakes. Intracellular nicotinate (alias vitamin B3) as well as low pH‐values of the external medium elevated [ 3 H]nicotinate accumulation into X. laevis oocytes, suggesting an nicotinate/nicotinate or nicotinate/OH − exchange mode for hORCTL3. A Michaelis constant (K m ) value of 44 μM for nicotinate indicates that hORCTL3 is the first molecularly identified high affinity nicotinate transporter in kidney and intestine.